Decreased expression of c-myc oncoprotein by peripheral blood mononuclear cells in thalassaemia patients receiving desferrioxamine.
Desferrioxamine (DFX) is an iron chelation agent widely used in the treatment of transfusional iron overload in patients with thalassaemia major and other severe refractory anaemias. DFX has been shown to induce inhibition of DNA synthesis and apoptosis in vitro; however, the molecular targets of DFX action are not well known. The c-myc proto-oncogene is involved in a number of cellular processes including proliferation, differentiation and apoptotic cell death. We have examined the expression of c-myc in peripheral blood mononuclear cells from 71 patients with homozygous beta-thalassaemia in regular transfusion and iron chelation therapy with DFX, 5 non-transfusion, non-chelation-dependent thalassaemic patients, and 15 healthy volunteers using an APAAP immunocytochemical method. We have found that mononuclear cells from thalassaemic patients receiving DFX express significantly lower levels of c-myc protein compared to control healthy volunteers or thalassaemics receiving no DFX. In vitro treatment of HL60 or K562 leukaemic cells with 100 microliters DFX also induced a rapid decrease in c-myc mRNA and protein levels, followed by apoptosis and inhibition of DNA synthesis. These effects were blocked by simultaneous addition of ferric chloride. Our data suggest that deprivation of cellular iron induces downregulation of c-myc expression in vitro and in vivo and may influence haemopoietic cell growth and survival.
Kyriakou
D
D
Department of Haematology of the University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Eliopoulos
A G
AG
Papadakis
A
A
Alexandrakis
M
M
Eliopoulos
G D
GD
D000293:Adolescent; D000328:Adult; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007223:Infant; D007501:Iron; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D017086:beta-Thalassemia / Q000188:drug therapy*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D007501:Iron; D003676:Deferoxamine